1. Field of the Invention
The invention relates to a process for the preparation of 1,3-dicarbonyl compounds. The process involves a condensation reaction of a ketone with either an ester or a carbonate to form, respectively, a 1,3-diketone or a .beta.-ketoester. Such 1,3-dicarbonyl compounds may be used as starting materials or intermediates for the synthesis of heterocycles, costabilizers for chlorinated polymers (e.g. polyvinyl chloride), or waste extractants (U.S. Pat. No. 4,175,012).
2. Description of the Related Art
Condensation reactions between ketones and esters are powerful methods for the preparation of 1,3-diketones, which are important synthetic intermediates for a variety of industrially important compounds such as herbicides. Several such compounds are isoxazole and derivatives thereof (Casado et al., WO 95/00476; and Cain et al., EP 470856). Though less reactive, a carbonate may be used in place of an ester to form a .beta.-ketoester by a condensation reaction. These condensations, generally known as Claisen condensations, are usually performed under basic conditions. In many cases, the reaction is facile, and can be effected using an alkoxide base. However, when the ester is hindered or a relatively unreactive carbonate is used, the reaction is much more challenging and offers poor yields.
The Claisen condensation is a well-known reaction, and there are many methods to affect this condensation reaction. (Hauser et al., Organic Reactions 8:59 (1954)). The standard conditions under which 1,3-dicarbonyl compounds can be generally prepared include the use of an alkoxide base in a standard organic solvent such as an alcohol, an aromatic hydrocarbon, or an ether. These conditions are quite sufficient when the electrophile is either a formate, an acetate or another highly reactive ester. However, when the ester becomes more hindered, such as, for example, an isobutyrate, or when a less-reactive carbonate is used, these reaction conditions often fail. In these cases, the desired reaction can sometimes still be affected using an alkoxide by conducting the reaction in a high-boiling solvent such as toluene or xylene at high temperature, often with continuous removal of the generated alcohol. (Hauser et al., Organic Reactions 8:59 (1954); Reuther et al., EP 697,390). Claisen condensations can also be very sensitive to the order of addition of the reactants or may require a precise product isolation protocol in order to obtain the optimal product yield. (Krbechek et al., WO 95/24372).
Bases such as sodium hydride, sodium amide, and sodium tert-butoxide in an ethereal solvent, which irreversibly form the enolate anion of the ketone, have been used to promote conversion of reactants to the desired product. (Hauser et al., Organic Reactions 8:59 (1954); Drewes et al., EP 454,624). The anion of dimethyl sulfoxide, generated from DMSO and sodium hydride, has also been used to perform the Claisen condensation. (Bloomfield, J. J., J. Org. Chem. 27:2742 (1962); Anselme, J. P., J. Org. Chem. 32:3716 (1967)). However, sodium hydride is an expensive and dangerously reactive chemical, as it can vigorously release hydrogen upon reaction with an acidic material, even moist air. The use of a more innocuous and less expensive base, sodium methoxide, in a mixture of DMSO and an inert organic solvent has also been described. (Drewes et al., U.S. Pat. No. 5,344,992).
However, the use of standard Claisen condensation conditions to prepare 1,3-dicarbonyl compounds can suffer from poor yields and numerous by-products, which complicate isolation of the desired product. Accordingly, there still exists a need in the art for a straightforward and efficient process for the preparation of 1,3-dicarbonyl compounds upon condensation of a ketone with either an ester or a carbonate. The reaction should be insensitive to addition order, provide good yields, and not require a precise product isolation protocol. The 1,3-dicarbonyl compound should be produced in high yield and high purity.